Coronary artery disease (CAD) and osteoporosis are two primary medical problems in post menopausal women. While estrogen/progestogen replacement therapy is recommended for prevention of bone loss, estrogens and progestogens have important and often opposing effects on a number of CAD risk factors. We propose a comprehensive and integrated three year evaluation of the effects of nine different treatment strategies on bone mass retention, endometrial status, gallstone formation and a number of CAD risk factors, as compared with a group of comparable controls. Experimental groups will include three estrogen only groups (hysterectomized women only), and six estrogen/progestogen groups to evaluate effects of dosage, mode of administration, type of progestogen and timing of hormonal administration on these parameters. The study will not only establish the effects on CAD risk factors including lipoprotein (VLDL, LDL, HDL and HDL subfractions, HDL2/3) and apolipoprotein (apoA-I, A-II, B) levels, fasting and post-challenge glucose levels, a number of coagulation parameters including indicators of coagulation, fibrinolysis and platelet aggregation, and blood pressure, but also on potentially important changes in the composition of lipoproteins. We will additionally examine effects on the density distribution of LDL particles and on levels and composition of LDL in subgroups of the study population. The results of the proposed studies will provide information to allow an informed decision on defining which strategy provides optimal protection against bone loss and endometrial hyperplasia, but minimal alteration of the beneficial cardiovascular effects of estrogen.